rs2241714

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_030578.4(B9D2):c.33A>G(p.Ile11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,613,570 control chromosomes in the GnomAD database, including 380,889 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I11T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.70 ( 38333 hom., cov: 31)

Exomes 𝑓: 0.68 ( 342556 hom. )

Consequence

B9D2
NM_030578.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.146

Publications

92 publications found

Variant links:

Genes affected

B9D2 (HGNC:28636): (B9 domain containing 2) This gene encodes a B9 domain protein, which are exclusively found in ciliated organisms. The gene is upregulated during mucociliary differentiation, and the encoded protein localizes to basal bodies and cilia. Disrupting expression of this gene results in ciliogenesis defects. [provided by RefSeq, Oct 2009]

B9D2 links:

TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM91 links:

ENSG00000255730 (HGNC:):

ENSG00000255730 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_030578.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a domain C2 B9-type (size 116) in uniprot entity B9D2_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in NM_030578.4

BP4

Computational evidence support a benign effect (MetaRNN=7.400341E-7).

BP6

Variant 19-41363487-T-C is Benign according to our data. Variant chr19-41363487-T-C is described in ClinVar as Benign. ClinVar VariationId is 261881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D2	NM_030578.4	MANE Select	c.33A>G	p.Ile11Met	missense	Exon 2 of 4	NP_085055.2	Q9BPU9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
B9D2	ENST00000243578.8	TSL:1 MANE Select	c.33A>G	p.Ile11Met	missense	Exon 2 of 4	ENSP00000243578.2	Q9BPU9
TMEM91	ENST00000539627.5	TSL:1	c.-30+12285T>C		intron	N/A	ENSP00000441900.1	F5GWC9
B9D2	ENST00000675972.1		c.33A>G	p.Ile11Met	missense	Exon 2 of 4	ENSP00000501911.1	Q9BPU9

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106611

AN:

151746

Hom.:

38297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.652

GnomAD2 exomes

AF:

0.643

AC:

161624

AN:

251252

AF XY:

0.643

show subpopulations

Gnomad AFR exome

AF:

0.838

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.542

Gnomad EAS exome

AF:

0.452

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.681

AC:

995851

AN:

1461706

Hom.:

342556

Cov.:

AF XY:

0.677

AC XY:

492577

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.836

AC:

27980

AN:

33474

American (AMR)

AF:

0.531

AC:

23754

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

13922

AN:

26134

East Asian (EAS)

AF:

0.478

AC:

18984

AN:

39698

South Asian (SAS)

AF:

0.614

AC:

52921

AN:

86248

European-Finnish (FIN)

AF:

0.724

AC:

38657

AN:

53414

Middle Eastern (MID)

AF:

0.597

AC:

3444

AN:

5768

European-Non Finnish (NFE)

AF:

0.698

AC:

776065

AN:

1111866

Other (OTH)

AF:

0.664

AC:

40124

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18671

37341

56012

74682

93353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19626

39252

58878

78504

98130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.703

AC:

106707

AN:

151864

Hom.:

38333

Cov.:

AF XY:

0.697

AC XY:

51707

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.833

AC:

34481

AN:

41416

American (AMR)

AF:

0.578

AC:

8804

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.539

AC:

1867

AN:

3466

East Asian (EAS)

AF:

0.445

AC:

2292

AN:

5154

South Asian (SAS)

AF:

0.615

AC:

2956

AN:

4806

European-Finnish (FIN)

AF:

0.716

AC:

7547

AN:

10536

Middle Eastern (MID)

AF:

0.592

AC:

173

AN:

292

European-Non Finnish (NFE)

AF:

0.684

AC:

46481

AN:

67944

Other (OTH)

AF:

0.650

AC:

1366

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1583

3166

4749

6332

7915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.675

Hom.:

114199

Bravo

AF:

0.698

Asia WGS

AF:

0.551

AC:

1912

AN:

3478

EpiCase

AF:

0.656

EpiControl

AF:

0.658

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Meckel syndrome, type 10 (3)

not specified (3)

not provided (2)

Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.070

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.064

MetaRNN

Benign

7.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-0.15

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.56

REVEL

Benign

0.081

Sift

Benign

0.19

Sift4G

Benign

0.11

PromoterAI

0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.21

Mutation Taster

=85/15

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over